Project Summary Preclinical rehabilitation studies in the chronic phase of upper extremity stroke recovery have demonstrated the capacity to improve independent joint control in individuals with severe impairment, by reducing the expression of abnormal shoulder abduction/elbow flexion coupling, or flexion synergy, following a science-based data-driven intervention approach. Two decades of quantitative motor systems research underpins the concept of systematically targeting independent joint control in this population. The leading hypothesis explaining stroke- related loss of independent joint control is the increased reliance on contralesional corticoreticulospinal tract for the production of movement in the affected arm. Partial restoration of independent joint control demonstrated in preclinical studies logically extend this hypothesis by attributing improved movement to optimized use of residual ipsilesional corticospinal tract likely originating in the ischemic penumbra. The anatomical circuit of residual ipsilesional corticospinal tract is the only neural pathway available for the production of independent joint control, or in functional terms, outward reaching against gravity. With neuroimaging studies of individuals with severe chronic stroke supporting this hypothesis, it brings to light the supposition that optimized use of penumbral corticospinal tract may be achieved early in recovery, specifically the critical period of neural plasticity, in individuals with severe initial motor impairment. Stroke practice guidelines conclude that individuals with severe initial motor impairment are in the greatest need of novel and efficacious rehabilitation interventions. Therefore, our central hypothesis is that administration of progressive abduction loading therapy, shown to elicit sustained improvements in individuals with severe chronic stroke, will augment conventional acute and subacute rehabilitation through improved reaching function and attenuated development of loss of independent joint control. To test this hypothesis, we will recruit individuals with severe initial motor impairment and administer progressive abduction loading therapy as adjuvant to conventional in-patient and day-rehabilitation. A comparison group of dosage-matched reaching practice without abduction loading will be utilized. Study participants will be evaluated at admission, weekly until discharge, and then every other month until 1 year following baseline. Between group comparisons will be made over the duration of the first year of recovery (Aim 1). Approximately half of the study participants will transition to day-rehabilitation following in-patient rehabilitation and continue to receive the study interventions. The effect of extending progressive abduction loading therapy into subacute recovery will be tested with the addition of a dichotomous variable of enrollment in day-rehabilitation or not (Aim 2). Efficacy and dosage data will provide a go-no-go signal for the future administration of a large-scale pivotal phase III clinical trial. Longitudinal data will determine if progressive abduction loading therapy attenuates the development of loss of independent joint control.